Thursday 9 October 2008
Epidemiological updates
Scientific Advances
Public Health Developments
Meetings and workshops
Request for Contributions
Seasonal Influenza – European Status
Text updated from: European Influenza Surveillance Scheme (EISS) Electronic Bulletin
Week 40 (2/10/2008-9/10/2008)
Summary: Levels of influenza activity in Europe are currently low, and all countries reporting no or only sporadic influenza activity this week. There have been sporadic laboratory confirmed cases of influenza across Europe in the past four weeks.
Epidemiological situation - week 40/2008: For the intensity indicator, the national network levels of influenza-like illness (ILI) and/or acute respiratory infection (ARI) were low in all of the 21 countries providing these data. For the geographical spread indicator, sporadic influenza activity was reported in Norway and Sweden and no activity in 20 countries. Definitions for the epidemiological indicators can be found here.
Virological situation - week 40/2008: The total number of respiratory specimens collected by sentinel physicians in week 40/2008 was 105, of which one was influenza virus positive (type A not subtyped in Spain).
Comment: There have only been sporadic laboratory confirmed cases of influenza reported to EISS in the last month. A number of these cases were reported to be infections acquired outside of Europe (e.g. a person returning from holiday in Africa). Therefore it is currently too early to say which virus type or subtype will become dominant in Europe this season.
Background: The spread of influenza virus strains and their epidemiological impact in Europe are being monitored by EISS in collaboration with the WHO Collaborating Centre in London (United Kingdom) and the European Centre for Disease Prevention and Control
in Stockholm (Sweden).
Links to general information from EISS:
General information on EISS, including background, membership and information on citing the EISS bulletin
Definitions of epidemiological indicators used by EISS
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Seasonal Influenza – Antiviral Resistance
Resistance to oseltamivir (Tamiflu) in some influenza virus samples
EU and global data updated at the end of September2008
In late January 2008, antiviral drug susceptibility surveillance of seasonal influenza viruses was carried out in Europe (the EU-EEA-EFTA countries) by the EU-funded VIRGIL network. The National Influenza Centres revealed that some of the A (H1N1) viruses circulating this season (winter 2007-8) are resistant to the antiviral drug oseltamivir through mutation at position 274 in the viral neuraminidase gene.
Analysis of 2898 A(H1N1) viruses from 25 European (European Union, EEA/EFTA) countries isolated between November 2007 and late July 2008 (data archived on August 6th) showed that 704 were resistant to oseltamivir, but retained sensitivity to zanamivir and amantadine. The data are shown as a figure with a linked table.
The proportion of A(H1N1) viruses that are oseltamivir resistant varied significantly across Europe. The highest proportion of resistant viruses to date have been in Norway where 184 (67%) of the 273 samples are resistant to oseltamivir, whereas no resistant viruses have been detected in five of the 25 countries.
Surveillance in previous years by the Virgil Project found <1% of circulating viruses to be resistant The predominant influenza A viruses in Europe in winter 07/08 were A(H1N1) viruses, antigenically similar to the A/Solomon Islands/3/2006 virus included in the 2007/08 N Hemisphere vaccine. As the season progressed influenza B viruses started to circulate and then predominated. There was only limited circulation of other influenza A in Europe. Further details on country to country virus distribution this season are available on the European Influenza Surveillance Scheme (EISS) weekly update as well as in Influenza News.
Following the observation of a high level of resistance to oseltamivir in the A(H1N1) viruses circulating in Norway, the Norwegian authorities notified their EU partners and the World Health Organization (WHO) of this situation at the end of January. The Norwegian Public Health Institute also published an advisory to doctors and the public. The country with the second highest proportion is now Belgium (53%) followed by France with 231 (47%) of 496 specimens showing the marker for oseltamivir resistance. This is then followed by the Netherlands and Luxembourg with proportions of 27% and 26% respectively. There is no evidence that the appearance of these new viruses are related to use of oseltamivir which is currently seemingly not widely prescribed in most European countries. ECDC is now working with the manufacturer and national authorities to gather more information on routine oseltamivir use in Europe.
Experts from the European Centre for Disease Prevention and Control (ECDC), the European Commission, the European Influenza Surveillance Scheme and the World Health Organization (WHO) are currently assessing the significance of the data from the EISS VIRGIL network. An interim European risk assessment has been published by ECDC and comments on this are welcomed to influenza@ecdc.europa.eu.
Global surveillance started immediately after the detection in Europe and is being coordinated by WHO, and evidence has been found of similarly resistant viruses in North America and the Far East. All data including that on the WHO web-site are updated at monthly intervals at present.
The latest global data were posted on September 29th 2008 and now WHO is showing data separately for the 2007/8 winter season (Last Quarter 2007 to March 2008) and the 2008 season (Table 1 Second Quarter 2008 to August 20th). At the global level the most recent notable finding was from South Africa where now all 129 influenza A/H1N1 specimens gathered since the start of the second Quarter 2008 and tested for antiviral resistance showed the marker of resistance. Their findings have been confirmed by WHO Collaborating Centres. To date there have been 161 specimens influenza A/H1N1 specimens tested from WHO’s Africa Region but only ten of these have shown the markers of resistance apart from those from South Africa. Other significant national proportions of A/H1N1 specimens for the Southern Hemisphere or Equatorial regions showing resistance for which there are data are from Australia (25 out of 26), the Phillipines (10 out of 11) and the Hong Kong Region of China 97 out of 483 (17%). The finding of these viruses in the Southern Cone of South America in Chile (6 out of 44) and Argentina (11 out of 25) is considered significant as this is the part of the world that is usually last affected when other new influenza A viruses spread.(1)
Looking back to the earlier period (Quarter 4 2007 to end of Quarter 1 2008 equivalent to the Northern Hemisphere winter season where there are data on more than 50 specimens the results are: the Russian Federation 45%, (58 of 128), Canada 26% (127 of 486), United States 12% (126 of 1026), Japan 3% (44 of 1652), Hong Kong 12% (98 of 797), Australia 4% (3 of 83), Madagascar (none of 59), Korea (none of 99%) and New Zealand (none of 88). As well as the WHO monthly table. WHO is publishing less frequent analytic summaries on the WHO web-site. WHO also published regular summaries on influenza in the world. The last of these was published in late July. These data are interesting because they firstly indicate that these A(H1N1) viruses are not going away and also that they seem to be following the pattern suggested for A(H3N2) viruses of spreading eventually to even the Southern Cone of South America.(1) Although sporadic low level transmission of drug resistant viruses may have taken place since 1999 when the Neuraminidase Inhibitor drugs first were licensed, the 07/08 winter season is the first time there has been widespread and sustained transmission of such viruses in the community. Similar viruses have been seen before, but usually following treatment. Such viruses previously have not been able to readily transmit and have rapidly disappeared. Clinical experience in Norway and elsewhere suggests that people who become ill with an oseltamivir resistant strain of A(H1N1) have a similar spectrum of illness to those infected with “normal” seasonal influenza A which can cause severe disease or death in vulnerable people (older people, those with debilitating illnesses and the very young). This is now being investigated in national studies and international studies coordinated by ECDC.
At this stage the significance of these findings remains uncertain. The emergence of drug resistance in the context of limited drug use is unexpected, and the extent of future circulation is difficult to predict. ECDC, and the WHO Regional Office for Europe organised a Global Consultation in September with attendance from the WHO Global Programme on Influenza, the Four Global Influenza Collaborating Centres, the Community Network Reference Laboratory , VIRGIL, the European Commission and authorities in the most affected EU member states. Reports from that meeting are now being prepared along with a number of papers going towards peer-reviewed journals. These will be reported through this and other relevant web-pages.
It cannot be predicted whether these viruses will return to Europe this coming season. It is unusual to have one A(H1N1) dominated season following another, but everything about these viruses has been predictable. However surveillance is in place through the MS and the CNRL. A summary of the arrangements for the EU EEA & EFTA Countries is on the ECDC web-site this is also available in a pdf version as a briefing for policy makers in the EU and EEA/EFTA Member States.
(1) Russell C, Jones T, Barr I et al The global circulation of seasonal influenza A (H3N2) viruses Science 2008; 320 340-
AVIAN INFLUENZA
There are fluctuating reports in the media of influenza A(H5N1) and other avian influenza infections in birds and humans. ECDC monitors these carefully as part of its epidemic intelligence work. However without laboratory confirmation ECDC only rarely mentions these media reports in this output.
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AVIAN INFLUENZA – HUMAN HEALTH
9th October 2008
There are no new human cases of avian influenza A(H5N1) reported by WHO since 10th September 2008
Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO(10/09/2008)
H5N1 avian influenza: timeline of major events (10/09/2008)
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AVIAN INFLUENZA – ANIMAL HEALTH
10th October 2008
The German authorities have confirmed the presence of highly pathogenic A(H5N1) in a mixed poultry holding containing approximately 1500 poultry. All birds on the farm have been culled, and the containment measures taken in accordance with EU veterinary legislation.
Investigations into the source of the outbreak are ongoing.
ECDC Comment (2008-10-10): This is the first case of A(H5N1) to be reported within the EU in 2008. Investigations into the source of the outbreaks are ongoing, and it is premature to speculate on what that might be. However, there have been no cases reported from ongoing surveillance activities in wild birds in the EU, and hence there is little to suggest that the virus is widely disseminated within the EU at the current time. Currently the H5N1 virus remains primarily an infection of birds and current evidence suggests that all H5N1 viruses identified to date remains poorly adapted to humans. Hence the risks to public health remain very low. However, it remains important for people who may be considered to be at risk, such as those who keep poultry, to take sensible precautions to minimise the already very low risk of infection.
Press release from German State of Saxony on the outbreak (in German)
See:
ECDC Technical report: Who is at risk of getting Highly pathogenic H5N1 avian influenza in Europe? (May 2006)
ECDC Technical report: The Public Health Risk from Highly Pathogenic Avian Influenza Viruses Emerging in Europe with Specific Reference to type A/H5N1 (Version June 1st 2006)
Scientific advances
SCIENTIFIC ADVANCES – INFLUENZA VACCINES
Success and problems with live (non-injected) nasal vaccines for seasonal vaccines in young children
Safety and efficacy of live attenuated influenza vaccine in children 2-7 years of age
R.B. Belshe, C.S Ambrose and T.Yi
Description: This publication summarises the results of three trials of the new live attenuated influenza vaccines (LAIV) given nasally to young children. Two are controlled studies versus placebo and one is a trial comparing LAIV against conventional injected trivalent inactivated influenza vaccine (TIV). The publication pays particular attention to analyses the safety and efficacy of LAIV in the children of 2 years of age and older as this the age group for which LAIVs have been licensed. In the two placebo trials there was good efficacy demonstrated compared with placebo in children aged 2–7 years in seasons with matched strains, (69.2% [95% CI: 52.7, 80.4] and 94.6% [95% CI: 88.6, 97.5]). When compared with TIV recipients, children who had LAIV recipients and aged 2–5 years had about 50% fewer cases of confirmed influenza illness and this difference was statistically significant. In the children of two years and older the only adverse reactions noted were minor runny nose, nasal congestion and some low-grade fever. However the trials also involved children under age 2 and here problems arose. In the trial against injectable vaccines the LAIVs were associated with an excess of hospitalizations (for a variety of reasons) and medically significant wheezing were increased in children 6–11 and 6–23 months of age who received LAIV, respectively (compared to those receiving the injected vaccine). No such effect was seen in the older children.
ECDC Comment: (09/10/08) Children have many immunisations by injection in their first two years of life. Injecting a baby may not be a pleasant experience for baby, parent or the injector. Therefore the live nasal vaccines have been considered a very attractive prospect by those recommending influenza vaccination in children. The unexpected finding of an increase in hospitalisations for non-specific reasons has therefore been a considerable disappointment. The finding of significant wheezing following an oral live vaccine is not so unexpected. The set-back is especially unfortunate in that it’s the youngest children under age 3 (and those with other chronic diseases) that seem to be those most needing influenza immunisation as they are the age group in children at highest risk of experiencing severe disease in at least one European country(1) and in North America.(2)
- Heikkinen T, Silvennoinen H, Peltola V et al Burden of influenza in children in the community. JID 2004; 190: 1369-1973.
- Glezen WP, Taber LH, Frank AL, Gruber WC, Piedra PA. Influenza virus infections in infants. Pediatr Inf Dis J, 1997; 16: 1065-8.
- Fiore, AE, Shay DK, Haber P, Prevention and control of influenza. Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2007. MMWR Recomm Rep, 2007. 56(RR-6): p. 1-54.
Comment to influenza@ecdc.europa.eu
Recent trends in vaccine coverage in the elderly in France, Germany, Italy, Spain and the UK 2001/2 to 2006/7
Influenza vaccination coverage rates in five European countries during season 2006/07 and trends over six consecutive seasons. Blank P.R. Schwenkglenks M, Szucs TD. BMC Public Health. 2008 Aug 1;8:272. http://www.biomedcentral.com/1471-2458/8/272
Description: This article from the group that has been undertaking consumer surveys in EU countries since 2001/2 describes their experience over the six year period in the five countries where the work has been longest running. The work is supported by industry but is undertaken by a highly regarded University group and appears in peer-reviewed publications. The surveys were undertaken by applying a standard questionnaire telephoning the public (apart from in France where questionnaires are mailed). Unlike systems using administrative methods (returns from health services) this approach allows the investigators to also ask about attitudes to immunisation and the main sources of advice. Looking at overall coverage in the population the surveys found that in 2006/7 the coverage was between 22% and 25% with a slight overall upward trend from 2001/2 onwards. However in the most numerous ‘risk group’ – older people - there were no significant trends – uptake seems to have plateaued in these countries above the World Health Assembly target of 50% by 2006 but below that of 75% by 2010.(1) Rates of immunisation among those with chronic illness (which only started to be measured in 2003/4) were lower than for the elderly with the highest rates in 2006/7 in the UK and the lowest in Germany. Being both elderly and having a chronic illness increased the likelihood of being immunised in all four countries. The most commonly cited reason for getting immunised was the recommendation of the health care provider. Immunisation uptake among health care workers was also investigated and found to be low and not increasing except in France. In 2006/7 it ranged from 12% in Italy to 22% in Germany.
ECDC Comment: (09/10/08) There is a wealth of data in these surveys and the results are most interesting. For example the finding that being older and having a chronic illness boosts the likelihood of being immunised must have implications for interpretation of observational studies of vaccine effectiveness in the older people. It means people being immunised already have an expectation of ill-heath and so vaccine effectiveness in preventing severe illness in these countries at least will tend to be immunised. Also there is notable peak in the proportion of the population immunised in season 2005/6 across all countries, perhaps associated with the concern that season over ‘bird flu’ in the media and hence the general population (the effect is hardly there in older people). It is also ironic that though health workers are cited as the most powerful source of positive advice and encouragement by those being immunised many of these health workers seem to lack enthusiasm themselves in being vaccinated. However a difficulty is the validity of the values for vaccine coverage. Some are at variance with national figures. For example the cited figure from this work for the UK coverage in older people (over age 64 years) in 2006/7 season is around 65% while the official figures from that country reported by the national authorities to the VENICE survey and using administrative returns was 74%.(2) The confidence intervals overlap, but only just. There have been one publication comparing the results of the two systems in the UK and finding they correlated well but that does not look the case here.(3) Also would the results be put forward for publication if they did not agree. Probably more attention should be paid to the trends rather than the absolute values but it is useful to have another figure apart from the official returns as when the two agree we have greater confidence in the official findings and when they differ it is a trigger to looking at both systems. It is therefore saddening to learn that these valuable surveys may have to cease because of funding coming to an end.
1. Resolution of the World Health Assembly 56th Assembly WHA 56.19 Agenda Item 14.14 Prevention and Control of Influenza Pandemics and Annual Epidemics May 28th 2003 http://www.who.int/gb/ebwha/pdf_files/WHA56/ea56r19.pdf
2. VENICE & ECDC Project National seasonal influenza vaccination survey in Europe 2007. (in press will be posted on VENICE web site http://venice.cineca.org/
2. Muller D, Nguyen-Van-Tam JS, Szucs TD: Influenza vaccination coverage rates in the UK: a comparison of two monitoring methods during the 2002–2003 and 2003–2004 seasons. Public health 2006, 120(11):1074-1080
Comment to influenza@ecdc.europa.eu
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Public Health Developments
P.H. DEVELOPMENTS – PANDEMIC INFLUENZA - PREPAREDNESS
The UK Health Department, Scientific Pandemic Influenza Sub-Group on Modelling update to their Modelling Summary document.
Description: The UK Department of Health in London convenes a group of modellers chaired by Dr Peter Grove that have a particular interest in influenza and these come to an evidence-based agreement on how they would expect a pandemic would behave. This is the source of the UK’s pandemic planning assumptions. The group’s advice is based on both the available evidence from prior pandemics and modelling work.
For some time the Department of Health has been publishing at intervals summary papers which not only contains statements of what might happen but also the group’s view of the policy implications. This takes the form of notes on ‘What we can do now’ and ‘Policy questions’. The factors such as practicality, proportionality and questions of value for money are outside the remit of the sub-group and that is not cover in the particular document. The Department of Health has recently issued their most recent modelling Summary document and that can be found on the DH website.
Topics covered in the document include how the pandemic is likely to spread in the UK, the national and local pandemic profile, and its more likely impact on the population, as well as the expected effectiveness of pharmaceutical and non-pharmaceutical countermeasures.
ECDC would be interested to learn of other similar initiatives by authorities in Europe, especially if they are in the public domain.
Comment to influenza@ecdc.europa.eu
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P.H. DEVELOPMENTS – INFLUENZA
Influenza Vaccination - new section on the ECDC web-site
and Publication of VENICE project results on Seasonal Influenza Coverage in the Elderly for the EU/EEA member States
The area dealing with influenza on the ECDC web-site has up to now been divided into three Avian Influenza, Pandemic Influenza and Seasonal Influenza each leading onto ECDC publications, Questions and Answers, Fact Sheets. From this week there will be a fourth section Influenza Vaccination through which it is possible to find ECDC’s scientific opinion on seasonal influenza risk groups, its guidance on human avian influenza ‘pre-pandemic’ vaccines and lists of all the scientific and public health developments relating to influenza vaccination featured in influenza news.
This development coincides with publication of the results of the VENICE Project’s 2007-8 survey on coverage of seasonal influenza vaccine coverage in older people in Europe as a Rapid Communication in Eurosurveillance and a publication of a press release from ECDC emphasising the importance of seasonal influenza immunisation programmes which are underway at present in most Member States and announcing the start of weekly surveillance through the EISS system.
Comment to
influenza@ecdc.europa.eu
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P.H. DEVELOPMENTS –AVIAN INFLUENZA-INNOVATIONS
One Health – an initiative which designed to unite human and veterinary medicine concerning Zoonoses
Description: With the beginning of October new “One Health” website was launched. One Health is a concept mostly from the veterinary world with particular relevance to zoonoses (animal infections that can infect and affect humans) including avian influenza. The developers envision this website as a method of providing worldwide ‘One Health’ Initiative information for the general public, political and governmental leaders, news media and all ‘One Health’ professionals, advocates and supporters. The 'One Health Newsletter' and its links will be prominently featured on the site as a major 'One Health' international educational publication. In addition, there will be links to the American Veterinary Medical Association 'One Health' task force recommendations published in the Journal of the AVMA (JAVMA) and other pertinent 'One Health' publications. The website is a first part of One Health concept which is a worldwide strategy for expanding interdisciplinary collaborations and communications in all aspects of health care for humans and animals.
ECDC comment: The development and launch of this site is associated with the forthcoming International Ministerial Conference on Avian and Pandemic Influenza in Sharm el-Sheikh, Egypt. Avian influenza is the most eye-catching zoonosis at present but of course there are many others such as rabies, some of the viral haemorrhagic fevers and many food borne infections (salmonella, campylobacter spp etc.) Cooperation has been especially strong over avian influenza and it will be interesting to see how this is captured in the One Health concept. To date most of the support for this has come from the veterinary world and it now needs to be picked up also by the medical specialists if it is to have enduring value.
To visit the One health Website click here: http://www.onehealthinitiative.com
Comment to influenza@ecdc.europa.eu
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Meetings and workshops
International Ministerial Conference on Avian and Pandemic Influenza, Sharm el-Sheikh, Egypt. 24-26 October 2008.
This meeting organised by the Government of Egypt is the sixth in a series of high level meetings that began in Washington in October 2005, followed by Beijing (January 2006), Vienna (June 2006) Bamako (December 2006) and Delhi (November 2007). The Delhi meeting established a Road Map for countries to progress AI prevention and pandemic planning during 2008.
The Ministerial meeting in Egypt is supported by many bodies including the European Union, United Nations, WHO, United States international aid (USAID), the World Bank, the two major global animal health organisations (OIE & FAO) and the African Union. The focus is to assess the current epidemiological situation and progress since Delhi, and review the effectiveness of the strategies applied and remap the way forward in global avian and pandemic flu preparedness and response for 2009. A group from the UN Development programme (UNDP) is in the process of preparing a report for the meeting. Its last report is available at http://www.undg.org/docs/8097/12-18-07-UN-WB-AHI-Progress-Report-final.doc
A web-site for the conference in Egypt has now been activated http://www.imcapi2008.gov.eg/
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Retroscreen Virology Conference - Medical, Scientific and Historical Lessons from the Great Avian (H1N1) "Spanish" Influenza Pandemic of 1918:The 90th Anniversary 10th November 2008 at The Imperial War Museum - London
This conference specifically considers the first World War and the start of the Spanish Influenza pandemic. Specifically did the war itself engender the emergence of this avian influenza A(H1N1)? Are there serious lessons from that pandemic to help today as we prepare for 21st century pandemics?
Details are at http://www.retroscreen.com/rv/news/rel/allnews_rel/2008/2008-09-08/
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International Workshop - Ethical Issues in European National Preparedness for Pandemical Influenza, Paris, 20-21 November 2008
A web-site with registration details are at http://www.espace-ethique.org/fr/pandemic_ethics_november_2008.php
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European Scientific Conference on Applied Infectious Disease Epidemiology, Berlin 19-21 November 2008.
The second annual European Scientific Conference on Applied Infectious Disease Epidemiology – ESCAIDE – is fast approaching. The event is being held in Berlin from 19-21 November, and over 500 health experts from across Europe and beyond are expected to come together to share scientific knowledge and experience on all areas related to infectious disease epidemiology.
It is possible to register for the conference for a reduced fee of 100 Euros- the deadline for early registration is 1st October. It is also still possible to submit a ‘late breaker abstract’ to the conference- the deadline for submission is 29th September.
Details of the full conference programme, participant registration, and abstract submission can be found on the ESCAIDE website
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International symposium on viral respiratory disease surveillance. Seville, Spain 25-27th March 2009. International Society for Influenza and other Respiratory Virus Disease (ISIRV)
Conference information can be found at http://www.isirv.org
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Contributions Requested
The ECDC influenza project team very much welcomes potential contributions to these web updates from EU/EEA member states particularly concerning public health developments and scientific published papers. This includes publications in non-English languages. These should be sent, preferably with a web-link, to influenza@ecdc.europa.eu. If drawing to our attention a non-English language article for development, a short summary in English is appreciated. However, this is not essential because of its multi-national staff, ECDC can cope with most languages from within the EU.